This application proposes to (a) define, localize and study the mode of action of genes involved in susceptibility/resistance to x-irradiation-induced (FXirrad) leukemia; (b) determine the role of viruses, if any, in the etiology of FXirrad-induced leukemia, and (c) attempt to understand how radiation-induced leukemia virus (RadLV) deregulates expression of major histocompatibility complex (H-2) coded antigens thereby rendering mice resistant to the disease. Toward these goals we intend to precisely map by three point genetic analyses the loci conferring resistance/susceptibility to radiation-induced leukemia that are associated with chromosomes 1 and 4. Precise mapping would help evaluate whether xenotropic-related loci XenCSA and Bxv - 1 play a role in the etiology of FXirrad-induced leukemia. Major emphasis will be placed on studying the function of Ril-1 a locus conferring overall resistance to FXirrad-induced leukemogenesis. Ril-1 is centromeric to Ly-11 on chromosome 2. To study the function of Ril-1 we shall (a) develop a congenic strain pair differing only in their Ril-1 alleles; (b) determine whether Ril-1 is involved in resistance to RadLV; (c) attempt to identify Ril-1 gene product(s) by serological means; (d) study the effect of Ril-1 on virus induction by FXirrad; (e) determine whether Ril-1 associated mechanism(s) act at a differentiation specific step by blocking transfection of proviral DNA into established lymphoma lines, and (f) if (a)-(e) fail to identify Ril-l's function, study possible effects of this locus on humoral nd cellular immunity. To address the third issue we shall (a) clone RadLV such that a specific probe can be made to study its integration into murine DNA, and (b) compare H-2 genes of normal and RadLV infected and transformed thymocytes using an H-2 specific probe (kindly provided by Dr. Steinmetz at Cal Tech) to determine whether structural alterations or rearrangements have occurred which could alter the rate of H-2D transcription.